IFIBYNE   05513
INSTITUTO DE FISIOLOGIA, BIOLOGIA MOLECULAR Y NEUROCIENCIAS
Unidad Ejecutora - UE
artículos
Título:
The 5-HT5A receptor regulates excitability in the auditory startle circuit: functional implications for sensorimotor gating
Autor/es:
CURTIN, PAUL C.; MEDAN, VIOLETA; NEUMEISTER, HEIKE; BRONSON, DANIEL; PREUSS, THOMAS
Revista:
JOURNAL OF NEUROSCIENCE
Editorial:
SOC NEUROSCIENCE
Referencias:
Lugar: Washington; Año: 2013 vol. 33 p. 10011 - 10020
ISSN:
0270-6474
Resumen:
Here we applied behavioral testing, pharmacology, and in vivo electrophysiology to determine the function of the serotonin 5-HT5A
receptor in goldfish startle plasticity and sensorimotor gating. In an initial series of behavioral experiments, we characterized the effects
of a selective 5-HT5A antagonist, SB-699551 (3-cyclopentyl-N-[2-(dimethylamino)ethyl]-N-[(4-{[(2-phenylethyl)amino]methyl}-4-
biphenylyl)methyl]propanamide dihydrochloride), on prepulse inhibition of the acoustic startle response. Those experiments showed a
dose-dependent decline in startle rates in prepulse conditions. Subsequent behavioral experiments showed that SB-699551 also reduced
baseline startle rates (i.e., without prepulse). To determine the cellular mechanisms underlying these behaviors, we tested the
effects of two distinct selective 5-HT5A antagonists, SB-699551 and A-843277 (N-(2,6-dimethoxybenzyl)-N[4-(4-fluorophenyl)thiazol-
2-yl]guanidine), on the intrinsic membrane properties and synaptic sound response of the Mauthner cell (M-cell), the decision-making
neuron of the startle circuit. Auditory-evoked postsynaptic potentials recorded in the M-cell were similarly attenuated after treatment
with either 5-HT5A antagonist (SB-699551, 26.413.98% reduction; A-843277, 17.526.24% reduction). This attenuation was produced
by a tonic (intrinsic) reduction in M-cell input resistance, likely mediated by a Cl conductance, that added to the extrinsic inhibition
produced by an auditory prepulse. Interestingly, the effector mechanisms underlying neural prepulse inhibition itself were unaffected by
antagonist treatment. In summary, these results provide an in vivo electrophysiological characterization of the 5-HT5A receptor and its
behavioral relevance and provide a new perspective on the interaction of intrinsic and extrinsic modulatory mechanisms in startle
plasticity and sensorimotor gating.